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Silicosis is a disease caused by prolonged exposure to silica dust. It is the most typical, rapidly progressive, and fatal form of pneumoconiosis. Currently, there is no specific medication available for the treatment of silicosis. LOXL2 is a copper-dependent lysine oxidase whose main function is to catalyze the cross-linking of extracellular matrix components, particularly collagen and elastin. However, few researchers have investigated the role of LOXL2 in the pathogenesis of silicosis. In this study, we demonstrated that LOXL2 is upregulated in silica-inhaled mouse lung tissue and in a TGF-β-induced fibroblast model. In vitro, we confirmed that LOXL2 functions to promote ECM deposition by binding directly to collagen and elastin. We then used scavenger receptor cysteine-rich (SRCR) domains to show that LOXL2 can induce fibrosis independently of its enzymatic activity. Furthermore, we discovered that NUDT21, the LOXL2 upstream regulatory mechanism of LOXL2, alters LOXL2's 3′UTR usage by substituting alternative polyadenylation (APA), thereby modulating LOXL2 expression. By injecting LOXL2 siRNA-loaded liposomes into the tail vein of mice in the silica dust-treated mouse pulmonary fibrosis model, the severity of lung fibrosis was significantly reduced. In this context, LOXL2 is regulated by NUDT21 and may affect pulmonary fibrosis by influencing the cross-linking of ECM proteins. Our research provides a scientific basis for the development of new anti-fibrosis treatment strategies.

BackgroundStudies have shown that more than half of the human genome expression is affected by circadian rhythms, which includes genes involved in cell cycle control, DNA repair and apoptosis that are critical in cancer biology. However, the roles of circadian rhythm-related genes (CRRGs) in cervical cancer (CC) and other common gynecologic cancers remain unclear.MethodsThe transcriptome data and clinical information related to CC and other common gynecologic cancers were extracted from the UCSC Xena and Gene Expression Omnibus (GEO) databases. In this study, the differentially expressed CRRGs of CC (target genes) were obtained, and the functional enrichment analysis of these target genes was performed by “clusterProfiler”. Then, the biomarkers of CC were screened out to construct the survival risk model (risk score). Moreover, function and tumor micro-environment (TME) analyses in different risk groups were performed for further study of the potential mechanism of CC. Furthermore, the prognostic value and function analyses of biomarkers in three common gynecologic cancers were performed to reveal the potential agreement or heterogeneity regulations.ResultsA total of 19 target genes were associated with pyrimidine metabolism. The survival risk model was constructed with six biomarkers, including APOBEC3B, CDA, HELLS, RHOB, SLC15A3, and UPP1. Among these, APOBEC3B, HELLS, and SLC15A3 were identified as positive factors, while CDA, RHOB, and UPP1 were identified as negative factors in CC. It is notable that multiple immune-related signaling pathways were associated with the clinical risk of CC, and the immunotherapy sensitivity was worse in the high-risk group. In addition, we found that most of biomarkers had the prognostic values in other common gynecologic cancers. It was notable that the mechanisms by which these biomarkers influence gynecologic cancers were associated with extracellular matrix (ECM) receptor interaction, focal adhesion, etc.ConclusionThis study identified six circadian rhythm-related biomarkers, including APOBEC3B, CDA, HELLS, RHOB, SLC15A3, and UPP1, which were associated with the prognosis of CC. The mechanisms by which these biomarkers influence gynecologic cancers were associated with ECM receptor interaction, focal adhesion, and other functions. These findings might help to deepen the understanding of the agreement or heterogeneity of CRRGs in the pathological processes of common gynecologic cancers.

Abstract Objectives The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients. Methods We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases. Results Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (p Oral_Sob < 0.001, p Oral_Shannon = 0.049, p Oral_Simpson = 0.013 p Fecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota (p Vaginal_Pielou = 0.028, p Vaginal_Simpson = 0.006). There were also significant differences in the β-diversity of the microbiota at each site between cases and controls (p Oral = 0.002, p Fecal = 0.037, p Urine = 0.001, p Vaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (p Urine = 0.036) and lymph node metastasis (p Urine_Sob = 0.027, p Urine_Pielou = 0.028, p Urine_Simpson = 0.021, p Urine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors. Conclusions Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.

Abstract Objectives The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. Methods Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. Results We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09–1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95–1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79–1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13–1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10–1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07–1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14–1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04–2.49, P = 0.032). The results of Begg’s and Egger’s tests showed no publication bias. Conclusions This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Nonstructural carbohydrates (NSC) are important substrates for plant growth and metabolism, and their concentration reflects the plant's ability to adapt to environmental changes. Although the response of NSC to changes in water availability has been extensively studied, it is still not fully understood whether this response is modulated by tree ages and organs. This study investigates Haloxylon ammodendron (C.A. Mey.) Bunge ex Fenzl, the dominant species in the Gurbantunggut Desert in the Uyghur Autonomous Region of China. Utilizing the natural topographic conditions characterized by a gradual increase in groundwater depth from the desert edge to the hinterland, we collected samples of different age classes of H. ammodendron along a groundwater depth gradient of 3, 7, 10, and 14 m. We measured the total concentrations of non-structural carbohydrates (NSC) and its components soluble sugar (SS) and starch (ST) in the assimilative twigs and stems. The results showed that the assimilative twigs of H. ammodendron exhibited higher NSC concentrations at the site with the deepest groundwater, while the other three sites showed similar NSC concentrations. Furthermore, as groundwater depth increased, the concentrations of SS in the assimilative twigs increased, whereas ST concentrations decreased. Similarly, the concentrations of SS in the stems also increased at sites with deeper groundwater. The NSC concentrations in the assimilative twigs were significantly affected by groundwater depth, while variations in stem NSC were primarily driven by plant age. In younger trees, higher soluble sugars concentrations in the stem may enhance water transport efficiency, whereas older trees tend to store more NSC to alleviate drought stress. Overall, elevated nonstructural carbohydrate concentrations contributed to greater drought resilience in H. ammodendron. These results suggest that different age classes of H. ammodendron exhibit distinct physiological responses to decreasing groundwater depth. The varying requirements for soluble sugars and starch in H. ammodendron help to partially mitigate the adverse effects of reduced groundwater accessibility. These findings provide important insights into the physiological adaptations of H. ammodendron in arid environments and offer a scientific basis for future ecological restoration and management strategies.

A thermodynamic model to predict the stacking fault energy (SFE) of Fe–Mn and Fe–Mn–C austenite steels based on the two-sublattice method has been developed. The calculated Gibbs free energy change, phase transformation temperature, and SFE are basically coincident with the experiment values. The interfacial energy during face center cubic to hexagonal close packed transformation was determined by a parabolic function of Gibbs free energy change in the concerned systems. The interstitial segregation and the resulting SFE in Fe–Mn–C steels have been clearly revealed. The carbon segregated concentration in the stacking faults is in good agreement with the measured value. Low SFE regions were observed to be located at 12 wt% manganese in the Fe–Mn binary system and at 14 wt% manganese in the Fe–Mn–C ternary system, respectively. The carbon- and manganese-dependent SFE maps were consequentially plotted under different temperatures and grain sizes. For the steels with manganese and carbon range between 10–30 and 0–1.2 wt%, the SFE increases monotonously with temperature increasing. The SFE of Fe–Mn–C steels decreases as grain size increases from 1 to 70 μm. However, for the alloys with more coarse-grained structures, the SFE sensitivity to grain size was not obvious.

Abstract Objective To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. Methods Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day’s 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. Results A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. Conclusions The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.

Plant hydraulic traits are essential for understanding and predicting plant drought resistance. Investigations into the mechanisms of the xylem anatomical traits of desert shrubs in response to climate can help us to understand plant survival strategies in extreme environments. This study examined the xylem anatomical traits and related functional traits of the branches of seven Calligonum mongolicum populations along a precipitation gradient, to explore their adaptive responses to climatic factors. We found that (1) the vessel diameter (D), vessel diameter contributing to 95% of hydraulic conductivity (D95), hydraulic weighted vessel diameter (Dh), vessel density (VD), percentage of conductive area (CA), thickness-to-span ratio of vessels ((t/b)2), and theoretical hydraulic conductivity (Kth) varied significantly across sites, while the vessel group index (Vg), wood density (WD), and vulnerability index (VI) showed no significant differences. (2) Principal component analysis revealed that efficiency-related traits (Kth, Dh, D95) and safety-related traits (VI, VD, inter-wall thickness of the vessel (t)) were the primary factors driving trait variation. (3) Precipitation during the wettest month (PWM) had the strongest influence, positively correlating with (t/b)2 and negatively with D, D95, Dh, CA, and Kth. (4) Structural equation modeling confirmed PWM as the main driver of Kth, with indirect effects through CA. These findings indicate that C. mongolicum displays high plasticity in xylem traits, enabling adaptation to changing environments, and providing insight into the hydraulic strategies of desert shrubs under climate change.

Abstract Background Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica. Methods We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of circZNF609, miR-145-5p, and KLF4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), Western blotting, immunofluorescence assays, and CCK8 were performed to investigate the role of the circZNF609/miR-145-5p/KLF4 axis and circZNF609-encoded peptides in fibroblast activation. Results Our data showed that circZNF609 was downregulated in activated fibroblasts and silica-induced fibrotic mouse lung tissues. Overexpression of circZNF609 could inhibit fibroblast activation induced by transforming growth factor-β1 (TGF-β1). Mechanically, we revealed that circZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and circZNF609-encoded peptides. Furthermore, circZNF609 was highly methylated and its expression was controlled by N6-methyladenosine (m6A) modification. Lastly, in vivo studies revealed that overexpression of circZNF609 attenuates silica-induced lung fibrosis in mice. Conclusions Our data indicate that circZNF609 is a critical regulator of fibroblast activation and silica-induced lung fibrosis. The circZNF609 and its derived peptides may represent novel promising targets for the treatment of pulmonary fibrosis.

In this study, four absolute nodal coordinate formulation (ANCF)-based approaches are utilized in order to predict the buckling load of Lee’s frame under concentrated load. The first approach employs the standard two-dimensional shear deformable ANCF beam element based on the general continuum mechanics (GCM). The second approach adopts the standard ANCF beam element modified by the locking alleviation technique known as the strain-split method. The third approach has the standard ANCF beam element with strain energy modified by the enhanced continuum mechanics formulation. The fourth approach utilizes the higher-order ANCF beam element based on the GCM. Two buckling load estimation methods are used, i.e., by tracing the nonlinear equilibrium path of the load–displacement space using the arc-length method and applying the energy criterion, which requires tracking eigenvalues through the dichotomy scheme. Lee’s frame with different boundary conditions including pinned–pinned, fixed-pinned, pinned-fixed, and fixed–fixed are studied. The complex nonlinear responses in the form of snap-through, snap-back, and looping phenomena during nonlinear postbuckling analysis are simulated. The critical buckling loads and buckling mode shapes obtained through the energy criterion-based buckling method are obtained. After the comparison, higher-order beam element is found to be more accurate, stable, and consistent among the studied approaches.

Abstract Background This study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum. Methods This study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model’s predictive value for predicting not returning to postpartum BP visit at each follow-up time point. Results In this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01–6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94–0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005–1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805–5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92–0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04–1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06–2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively. Conclusion Attendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.

Abstract Background Histomorphological differentiation between pancreatic serous cystadenoma (SCA) and clear cell renal cell carcinoma (RCC) can be challenging. We aimed to study Paired box 8 protein (Pax8) expression profile in cytologic and surgical specimens with pancreatic SCA to assess its utility as a differentiating marker from clear cell RCC. Methods We characterized Pax8 immunohistochemistry in 33 patients with pancreatic SCA (23 surgical resections and 10 cytology specimens). Nine cytology specimens from metastatic clear cell RCC involving pancreas were used as control tissue. Electronic medical records were reviewed to retrieve clinical information. Results All 10 pancreatic SCA cytology specimens, and 16 of 23 pancreatic SCA surgical resections showed absent Pax8 immunostaining, while the remaining 7 surgical resection specimens showed 1%-2% immunoreactivities. Islet and lymphoid cells adjacent to the pancreatic SCA expressed Pax8. In contrast, the proportion of Pax8 immunoreactivity ranged from 50 to 90% (average of 76%) in nine cases of metastatic clear cell RCC involving pancreas. Using a 5% immunoreactivity cutoff, all cases of pancreatic SCA are interpreted as negative for Pax8 immunostains while all cases of metastatic clear cell RCC involving pancreas are interpreted as positive for Pax8 immunostains. Conclusions These results suggest that Pax8 immunohistochemistry staining can be a useful adjunct marker to differentiate pancreatic SCA from clear cell RCC in clinical practice. To the best of our knowledge, this is the first large-scale study of Pax8 immunostaining on surgical and cytology specimens with pancreatic SCA.

Colorectal cancer (CRC) at advanced stages is rarely curable, underscoring the importance of exploring the mechanism of CRC progression and invasion. NOD-like receptor family member NLRP12 was shown to suppress colorectal tumorigenesis, but the precise mechanism was unknown. Here, we demonstrate that invasive adenocarcinoma development in Nlrp12-deficient mice is associated with elevated expression of genes involved in proliferation, matrix degradation, and epithelial-mesenchymal transition. Signaling pathway analysis revealed higher activation of the Wnt/β-catenin pathway, but not NF-κB and MAPK pathways, in the Nlrp12-deficient tumors. Using Nlrp12–conditional knockout mice, we revealed that NLRP12 downregulates β-catenin activation in intestinal epithelial cells, thereby suppressing colorectal tumorigenesis. Consistent with this, Nlrp12-deficient intestinal organoids and CRC cells showed increased proliferation, accompanied by higher activation of β-catenin in vitro. With proteomic studies, we identified STK38 as an interacting partner of NLRP12 involved in the inhibition of phosphorylation of GSK3β, leading to the degradation of β-catenin. Consistently, the expression of NLRP12 was significantly reduced, while p-GSK3β and β-catenin were upregulated in mouse and human colorectal tumor tissues. In summary, NLRP12 is a potent negative regulator of the Wnt/β-catenin pathway, and the NLRP12/STK38/GSK3β signaling axis could be a promising therapeutic target for CRC.

In order to reveal the combined influences of Rayleigh (Ra) number, Reynolds (Re) number and spanwise aspect ratio (B) on the flow pattern evolution and stability, and heat transfer of Poiseuille-Rayleigh-Bénard (PRB) convection, we presented a set of three-dimensional numerical simulations on PRB convection of air in the horizontal channels using commercial software Fluent in a range of 2 ≤ B ≤ 10, 0 ≤ Re ≤ 250 and 1.7 × 103 ≤ Ra ≤ 2.5 × 104. Various flow patterns are observed, including transversal rolls, longitudinal rolls, mixed rolls and wavy flow. The results show that the number of longitudinal rolls depends on B and Ra. The critical Rayleigh numbers for appearance and destabilization of the longitudinal rolls and the transversal rolls increase with increasing Re. With increasing B, the critical Rayleigh numbers for the primary and secondary instabilities will decrease and the critical Reynolds number also decreases. The heat transfer of PRB convection is enhanced with increasing Ra and B. A heat transfer correlation of the average Nusselt number with Ra and B is established.

Objectives: Cardiorenal syndrome type-3 (CRS-3) is an abrupt worsening of cardiac function secondary to acute kidney injury. Mitochondrial dysfunction is a key pathological mechanism of CRS-3, and empagliflozin can improve mitochondrial biology by promoting mitophagy. Here, we assessed the effects of empagliflozin on mitochondrial quality surveillance in a mouse model of CRS-3. Methods: Cardiomyocyte-specific FUNDC1-knockout (FUNDC1CKO) mice were subjected to CRS-3 prior to assessment of mitochondrial homeostasis in the presence or absence of empagliflozin. Results: CRS-3 model mice exhibited lower heart function, increased inflammatory responses and exacerbated myocardial oxidative stress than sham-operated controls; however, empagliflozin attenuated these alterations. Empagliflozin stabilized the mitochondrial membrane potential, suppressed mitochondrial reactive oxygen species production, increased mitochondrial respiratory complex activity and restored the oxygen consumption rate in cardiomyocytes from CRS-3 model mice. Empagliflozin also normalized the mitochondrial morphology, mitochondrial dynamics and mitochondrial permeability transition pore opening rate in cardiomyocytes. Cardiomyocyte-specific ablation of FUN14 domain-containing protein 1 (FUNDC1) in mice abolished the protective effects of empagliflozin on mitochondrial homeostasis and myocardial performance. Empagliflozin activated β-catenin and promoted its nuclear retention, thus increasing FUNDC1-induced mitophagy in heart tissues; however, a β-catenin inhibitor reversed these effects. Conclusions: In summary, empagliflozin activated Wnt/β-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance, ultimately improving mitochondrial function and cardiac performance during CRS-3. Thus, empagliflozin could be considered for the clinical management of heart function following acute kidney injury.

Abstract In principle, polymerization tends to produce amorphous or poorly crystalline materials. Efficiently producing high-quality single crystals by polymerization in solvent remains as an unsolved issue in chemistry, especially for covalent organic frameworks (COFs) with highly complex structures. To produce μm-sized single crystals, the growth time is prolonged to >15 days, far away from the requirements in practical applications. Here, we find supercritical CO2 (sc-CO2) accelerates single-crystal polymerization by 10,000,000 folds, and produces two-dimensional (2D) COF single crystals with size up to 0.2 mm within 2~5 min. Although it is the fastest single-crystal polymerization, the growth in sc-CO2 leads to not only the largest crystal size of 2D COFs, but also higher quality with improved photoconductivity performance. This work overcomes traditional concept on low efficiency of single-crystal polymerization, and holds great promise for future applications owing to its efficiency, industrial compatibility, environmental friendliness and universality for different crystalline structures and linkage bonds.

Abstract Background Magnesium sulfate (MgSO4) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8–3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO4 in patients with severe preeclampsia. Methods Patients with severe preeclampsia who received MgSO4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO4, and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration. Results A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time from start of MgSO4 infusion to blood draw for serum sampling) as independent risk factors for sub-therapeutic serum magnesium concentration (P

The genus Acrophialophora belongs to the family Chaetomiaceae. With the addition of new species and transferred species from other genera, the genus Acrophialophora has expanded. In this study, eight new species related to Acrophialophora were isolated from soil samples in China. Using muti-locus phylogenetic (ITS, LSU, tub2 and RPB2) analysis combined with morphological characteristics, eight new species (Acrophialophora curvata, A. fujianensis, A. guangdongensis, A. longicatenata, A. minuta, A. multiforma, A. rhombica, and A. yunnanensis) are described. Descriptions, illustrations, and notes of the new species are also provided.

Although P40 and P63 are both sensitive and specific for routine esophageal squamous cell carcinoma (SCC) diagnosis, we recently showed that P40 and P63 immunoreactivities were significantly lower in well-differentiated SCC than those in higher grade tumors. Therefore, a novel esophageal SCC marker, ideally performing better in well-differentiated SCC, is still needed. We characterized desmoglein 3 (DSG3) immunohistochemistry in esophageal SCC, esophageal adenocarcinoma, small-cell lung carcinoma, and large B-cell lymphoma, alongside P40 and CK5/6. The World Health Organization classification was used to grade tumors as well-differentiated (WD), moderately differentiated (MD), or poorly differentiated (PD). There were 20 WD, 26 MD, and 17 PD components among 39 esophageal SCC cases. All esophageal SCC components showed significant DSG3 immunoreactivity (mean, 80%; range, 30%–100%), and the proportions of DSG3 immunoreactive cells were higher in the WD and MD components than in the PD components. No esophageal adenocarcinoma cases showed more than 10% DSG3 immunoreactivity with only weak cytoplasmic staining. With a 5% immunoreactivity cutoff, DSG3 positivity was 100% in all 63 SCC components, 18% in adenocarcinoma cases, and 0% in small-cell lung carcinoma or large B-cell lymphoma cases. The overall DSG3 specificity was 94%. To the best of our knowledge, this is the first study to characterize DSG3 as a sensitive and specific marker for esophageal SCC.

Final electromagnetic stirring (F-EMS) is widely used in the billet and bloom continuous casting process because it effectively improves the as-cast quality. Numerous industrial trials on F-EMS have been conducted; however, the real melt flow and heat transfer characteristics at the crater end remain unclear. In this study, based on a round billet special steel continuous casting process, a coupled three-dimensional numerical model was developed to describe the F-EMS phenomenon. The flow and solidification behavior of the melt in the F-EMS region were obtained by a segmentation calculation model, and the Darcy source term method was employed to suppress the velocity within the mushy region. The effect of stirring current intensity and frequency on the electromagnetic field, melt flow, and heat transfer was investigated numerically. The model was validated using the measured data of magnetic flux density in the stirrer center and the strand surface temperature. According to the simulation results, with every 100 A increase in the current intensity, the maximal magnetic flux density increases by 19.05 mT. The electromagnetic force significantly increases with the increase in current intensity. With the increase in current frequency within 20-40 Hz, the magnetic flux density decreases slightly, whereas the electromagnetic force increases. Moreover, a swirling flow field in the stirrer region is observed under the rotary electromagnetic force, and the tangential velocity of melt increases with the increase in current intensity and frequency. Additionally, the swirling flow enhances the local melt heat transfer at the radial direction of the round strand. As the current intensity and frequency increase, the temperature of the melt in the liquid core decreases, and the center solid fraction at the F-EMS-implemented position increases accordingly.

The mushy zone refers to the region of the solid-liquid system where the temperature is between the liquidus and solidus temperatures. In this zone, the turbulence of the interdendritic flow is reduced by blockage of dendrites. The mushy zone coefficient (Amush) is an important calculating parameter in the continuous casting numerical simulation process, which strongly affects the prediction of fluid flow and solidification behavior in the mold zone. However, most researchers have neglected the influence of the mushy zone coefficient, and the correct expression of this coefficient is rarely found in the literature. Generally, the lower default value of 1×105 kg·m-3·s-1 is used in the model, which leads to unrealistic results. In this study, the relationship between the mushy zone coefficient and permeability was analyzed, and the expression of the mushy zone coefficient was proposed. A coupled flow and solidification numerical model was developed to evaluate the effect of the mushy zone coefficient on the melt flow and solidification phenomena in a bloom continuous casting mold. Results show that the higher the value of the mushy zone coefficient, the stronger the damping becomes, and the faster the velocity drops as melt solidifies. A relatively high value of the mushy zone coefficient generates a "banded" form of mushy zone sandwiched between the solid and liquid phases in the mold zone. When the mushy zone coefficient is at a lower value, a wider mushy zone is obtained and the melt cools down rapidly in the mold region. In addition, the temperature at free surface is relatively low with supercooling, and the solidified shell remelts locally. The model is validated through comparison with measurements of shell thickness on a breakout shell. The value of the mushy zone coefficient ranging from 1×108 to 5×108 kg·m-3·s-1 is suggested.

Surface-enhanced Raman spectroscopy (SERS) is a promising technology for sensitive optical sensors, generally using rough metal films. Here, Liu et al. synthesize high-quality graphene quantum dot films which offer a large SERS enhancement due to a strong light-matter interaction with Van Hove singularities.

The thermal regime and structural control between continuous caster offline and a reheat furnace has a significant impact on the cracking problem occurring during hot charging or hot rolling. The effect of the charging process on the characteristics of austenite transformation and sizes of reheated grains was experimentally analyzed using thermal simulation. The in situ observation results using a high-temperature confocal laser scanning microscope shows that film-like ferrite and Widmanstätten ferrite are present along the grain boundary with amounts of retained austenite when hot charged at 700℃ in the dual phase region for J55 steel, and the size and location of the austenitic grain remain constant after reheating to 1200℃. When warm charged at 600℃ in the single phase region, large amounts of ferrite and pearlite are observed, and austenite grains are clearly refined after reheating to 1200℃. It is also found that the austenitic grain can only be visibly refined when the transformed ferrite fraction is higher than 70% for SS400 steel hot charged at different temperatures using a muffle furnace. The grain refinement is more obvious when the transformed ferrite fraction is higher than the critical value.

C44H49Cl2Co3N6O12, Triclinic, P1̅, a = 9.7415(9) Å, b = 13.6440(14) Å, c = 17.5241(11) Å, α = 72.807(10)°, β = 83.019(9)°, γ = 72.246(9)°, V = 2450.6(5) Å3, Z = 2, Rgt(F) = 0.0700, wRref(F2) = 0.1505, T = 291(2) K.

Although NOD2 is the major inflammatory bowel disease susceptibility gene, its role in colorectal tumorigenesis is poorly defined. Here, we show that Nod2-deficient mice are highly susceptible to experimental colorectal tumorigenesis independent of gut microbial dysbiosis. Interestingly, the expression of inflammatory genes and the activation of inflammatory pathways, including NF-κB, ERK, and STAT3 are significantly higher in Nod2−/− mouse colons during colitis and colorectal tumorigenesis, but not at homeostasis. Consistent with higher inflammation, there is greater proliferation of epithelial cells in hyperplastic regions of Nod2−/− colons. In vitro studies demonstrate that, while NOD2 activates the NF-κB and MAPK pathways in response to MDP, it inhibits TLR-mediated activation of NF-κB and MAPK. Notably, NOD2-mediated downregulation of NF-κB and MAPK is associated with the induction of IRF4. Taken together, NOD2 plays a critical role in the suppression of inflammation and tumorigenesis in the colon via downregulation of the TLR signaling pathways.

Conjugated microporous polymers (CMPs) have attracted intensive attention owing to their permanent nanoporosity, large surface area and possibility for functionalization, however their application in energy storage suffers from poor conductivity and low hetero-atom content. Here, we demonstrate a hybrid of conjugated microporous polymers and graphene aerogel with improved conductivity. After treating at 800°C in NH3, the nitrogen content increases to 9.8%. The resulting microporous carbon exhibits a significant rise in supercapacitive performance up to 325 F g−1, 55% higher than pristine triazine-based CMPs, with energy density up to 12.95 Wh kg−1. Moreover, it has high stability with 99% retention after 10,000 cycles at 5 A g−1. The synergy of hierarchical porous structure, graphene-based conduction path and high percentage of hybridization with nitrogen ensures effective ion/electron transport and diffusion, making NH3-treated graphene aerogel/CMP hybrid a promising electrode material in high-performance supercapacitor.

Hepatocellular carcinoma (HCC) is a deadly human cancer associated with chronic inflammation. The cytosolic pathogen sensor NLRP12 has emerged as a negative regulator of inflammation, but its role in HCC is unknown. Here we investigated the role of NLRP12 in HCC using mouse models of HCC induced by carcinogen diethylnitrosamine (DEN). Nlrp12-/- mice were highly susceptible to DEN-induced HCC with increased inflammation, hepatocyte proliferation, and tumor burden. Consistently, Nlrp12-/- tumors showed higher expression of proto-oncogenes cJun and cMyc and downregulation of tumor suppressor p21. Interestingly, antibiotics treatment dramatically diminished tumorigenesis in Nlrp12-/- mouse livers. Signaling analyses demonstrated higher JNK activation in Nlrp12-/- HCC and cultured hepatocytes during stimulation with microbial pattern molecules. JNK inhibition or NLRP12 overexpression reduced proliferative and inflammatory responses of Nlrp12-/- hepatocytes. In summary, NLRP12 negatively regulates HCC pathogenesis via downregulation of JNK-dependent inflammation and proliferation of hepatocytes.

The static tensile behaviors of Fe-22Mn-0.7C TWIP steel and Q235 steel between 700 ℃ and 1300 ℃ were investigated by Gleeble-1500 thermo-mechanical simulator.The microstructure characteristic and fracture morphology were observed by optical microscopy,scanning electron microscopy,energy dispersive spectrometry and electron probe micro-analysis.The hot ductility and influenced mechanism were revealed based on the discussion of chemical composition,matrix phase volume fraction,grain size and solidification defects.It is found that the TWIP steel has a reduction in area lower than 40% in the temperature range of 700 ℃ to 1250 ℃,but its tensile strength is higher than that of Q235 steel.Fractographic results manifest intergranular fracture for the TWIP steel.Grain refinement and microsegregation descending in the TWIP steel are beneficial to increasing the hot ductility due to the improvement of matrix homogeneity.Besides,the tensile strength and reduction in area of the TWIP steel increase with increasing strain rate.

C44H49Cl2N6O12Zn3, monoclinic, P1̅ (no. 2), a = 9.7387(8) Å, b = 13.7034(12) Å, c = 20.2498(16) Å, α = 72.539(8)°, β = 82.872(7)°, γ = 72.157(8)°, Z = 2, V = 2452.3(4) Å3, Rgt(F) = 0.0604, wRref(F2) = 0.1392, T = 293(2) K.

C46H56Zn3N6O14, monoclinic, C2/c (no. 15), a = 10.6703(7) Å, b = 27.091(4) Å, c = 17.9132(16) Å, β = 96.246(8)°, V = 5147.4(10) Å3, Z = 4, Rgt(F) = 0.0647, wRref(F2) = 0.1865, T = 291(1) K.

As the extracellular nuclease of Aspergillus, S1 nuclease can split single and double-stranded DNA into oligo- or mononucleotides, while preferentially digests single-stranded nucleic acids. Furthermore, the existence of S1 can be the standard to identify Aspergillus and used to evaluate the severity of Aspergillosis. Herein, a simple and sensitive fluorescent sensing platform for S1 assay was developed based on the S1-induced DNA strand scission and the difference in affinity of graphene oxide (GO) for single-stranded DNA containing different bases. This platform was applied to monitor S1 activity and study the kinetics in real time. Results indicated that the detection limit is 0.5 U/mL. The Km and kcat at 45 °C, are 1.4 ± 0.12 μM and 0.6 min−1, respectively. Moreover, by monitoring the effect of chemical drugs on S1 activity, we found that 2 mM of erythromycin, sodium penicillin, carbenicillin disodium and ampicillin can inhibit S1 activity about 8%, 60%, 61% and 66%, respectively, while gentamycin sulfate is a stimulator. Overall, the assay platform based on graphene oxide quenched fluorescence probe is successfully constructed to study the enzymatic activity of S1 and used for screening antibiotics. Keywords: S1 nuclease, Fluorescence probe, Graphene oxide, Real time

In this study, a new compound, 4-(N)-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC), was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3 Da and a melting point of about 96°C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80–based solution is 12.86 kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 105-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58 minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio). DHA-dFdC also significantly inhibited the growth of Panc-1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas.

Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.

Temperature fluctuations exist on the slab surface due to unstable heat flux during repeated contact and departure between the hot slab surface and the relatively cold supporting rollers in the secondary cooling zone. Considering thermal oscillations,hot ductility test under different thermal conditions was carried out on J55 microalloyed steel. The results show that at a temperature higher than 850℃,the hot ductility under the oscillating condition is lower than that under the isothermal condition,but it is on the contrary when the temperature equals or falls below 850℃. By analyzing results from experiment and from literature comprehensively,for the microalloyed steel,it is inferred that there exists a critical temperature a bit higher than the Ae3 temperature. Above this critical temperature the hot ductility under the isothermal condition is higher than that measured by the more accurate oscillating way,while below it the result is opposite. This conclusion is meaningful to determine the straightening temperature for microalloyed steel production during continuous casting.

Based on the analysis of the channel capacity,the equation about the increase of the channel capacity was derived when one more pair of transmit and receive antennas were added.By analyzing this equation,a joint transmit and receive antennas selection algorithm with low complexity were proposed when there were the same number of RF chains at both of the transmitter and receiver side.The simulation results illustrate that the new algorithm outperforms the other existing algorithms with lower complexity and it approaches the optimal algorithm most.